Dr Loftus reviews two of his Presidental Poster Award-winning presentations from the American College of Gastroenterology Scientific Meeting on the efficacy and safety and the rapidity of symptom control of upadacitinib induction therapy among patients with moderate to severe ulcerative colitis.

Edward Loftus, MD, is a professor of medicine at the Mayo Clinic in Rochester, Minnesota.

TRANSCRIPT:

Hi, this is Ed Loftus. I'm a professor of medicine at Mayo Clinic in Rochester, Minnesota. I wanted to talk to you today about one of the posters that was presented at ACG. This was a poster on the U-ACCOMPLISH study.

Now at ACG, you may have heard Dr. Higgins present the other phase 3 induction study for ulcerative colitis with upadacitinib, and that was the U-ACHIEVE phase 3study. This was the other induction study, the U-ACCOMPLISH study. These 2 trials were basically identical design.

These were patients with moderate-to-severe UC, and they were randomized in a 2-to-1 fashion to either upadacitinib 45 milligrams daily or placebo. Now recall that upadacitinib is a selective JAK1 inhibitor and is already approved for rheumatoid arthritis.

It's been shown in a phase 2 study in Crohn's disease to be promising, and this is the part of the phase 3 program in ulcerative colitis. Patients were assessed at the end of the induction trial, which was at week 8.

We're not going to talk about the maintenance trial today. The primary aim was clinical remission at week 8, and this was based on the adapted Mayo score.

There's no physician global assessment, and the stool frequency subscore had to be 0 or 1, not greater than baseline, and the rectal bleeding score had to be 0, and the Mayo endoscopic subscore had to be 0 or 1.

There were also secondary endpoints including endoscopic improvement, and endoscopic remission, clinical response at week 8, and clinical response per partial adapted Mayo score at even week 2.

You can see that over 500 patients were randomized in this trial to the 2 treatment arms, and most patients completed the trial. The baseline demographics were similar in both groups.

Roughly half of the patients had failed a biologic or were intolerant to a biologic, and that included roughly half on an anti-TNF and roughly a quarter on vedolizumab. Baseline corticosteroid use was in roughly 30 to 40% of the patients.

When you look at the figures in the poster, clinical remission, which was the primary endpoint at week 8, was met in a resounding fashion.

The treatment difference was 29%. It was 33 percent in the upadacitinib-treated patients and only 4% in the placebo treated patients. Clinical response was also robust, with 49% treatment difference.

Then, when you look at the clinical response per Adapted Mayo Score over time -- this is basically looking at stool frequency and rectal bleeding -- the treatment effect occurs early. Even by week 2, there's already a significant difference. You're talking about 63% versus 26% at week 2 for clinical response.

For some of the other ranked secondary endpoints, endoscopic improvement, the treatment difference was 35%. For endoscopic remission, the treatment difference was 16%. For the HEMI, which is histologic and endoscopic mucosal improvement, was also a significant difference of roughly 30% at week 8.

Also, marked reductions in CRP. The average CRP reduction was 6.2 in upadacitinib versus 2 in placebo. Fecal calprotectin, the average reduction in upadacitinib was over 2,000, whereas, in the placebo, it was about 500.

Adverse events occurred, though overall a pretty favorable safety profile. Considering the treatment effect, serious adverse events were numerically lower in the upadacitinib group, 3.2% versus 4.5% in placebo. Adverse events leading to study discontinuation were again lower with upadacitinib, 1.7% versus 5.1%.

The most common side effect was acne in 7% of patients on upadacitinib, and then CPK elevation in 4.7%. Anemia occurred in about 4% of patients.

This is looking very favorable as a treatment option for UC. As you know, the maintenance study was also presented at ACG as a late breaker, also looking very positive. We're looking forward, hopefully sometime next year, we'll have this as a treatment option available in our UC patients.

The other poster that I wanted to talk to you about on upadicinib had to do with the rapidity of response. I already alluded to that in that poster, but this poster was looking at rapidity of symptom control in the 2 induction trials. Again, identical induction trial designs.

We're not going to go over the endpoints again, but when you look at both of the induction trials and look at clinical remission at week 2, clinical response at week 2, still frequency score less than or equal to 1 at week 2, rectal bleeding score at 0 in week 2, you're seeing marked significant differences improvements over placebo at week 2.

The same results we're seeing in the U-ACCOMPLISH trials. Both induction trials, we're seeing marked improvements and in as early as week 2.

We haven't done the deep dive yet into the symptom diaries. I'm sure we'll see that at some point so we may be able to even break out still frequency in rectal bleeding at day whatever. It's very promising that by week 2 study visit, we're seeing these significant differences.

We talked about this a little bit already. There's already marked reductions in CRP and fecal calprotectin as early as week 2 in both of these groups. This is very promising. It reflects that it's not only an efficacious drug, but it's a rapidly acting drug, and for ulcerative colitis patients, we often need that. Thank you.